Carrageenan-induced inflammation in rat pleural cavity was used as a model to study how cellular activity is altered by anti-inflammatory drugs during the inflammatory response. Although at early stages of the response the pleural exudate contained a relatively high proportion of "mast cells" and high levels of intracellular histamine, there was no evidence from studies with antihistamine drugs and Compound 48/80 that histamine was involved in this reaction. At later stages (2-8 hrs.), neutrophils appeared in large numbers (1-2 times 10 to the 8th power cells) in the cavity and their number increased in the circulation. Thymidine-labelling experiments indicated that the cells were derived from bone marrow and were 2- to 3-days old. Treatment with nonsteroid anti-inflammatory drugs produced a marked decrease (60-75 percent) in the number of neutrophils appearing in the exudate without affecting the turnover or release of white cells in bone marrow and lymphoid organs. In contrast, methotrexate and dexamethasone were not anti-inflammatory unless given for 3 to 5 days, when the number of granulocytes and lymphocytes in tissue and circulation were decreased by more than 70 percent. The nonsteroid anti-inflammatory drugs appear, therefore, to inhibit the recruitment of white cells from the circulation.